Background and Aims: We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels ≤60 µg/dl, 81.2% had ferritin ≤100 ng/ml, and 25.6% had hemoglobin (Hb) of ≤12 g/dl (females) or ≤13 g/dl (males). In the treatment subcohort (n = 80), 83.1% of the patients had iron ≤60 µg/dl, 90.4% had ferritin ≤100 ng/ml, and 66.7% had Hb ≤12/13 g/dl before ferric carboxymaltose treatment. After a median dose of 500 mg ferric carboxymaltose, 74.7% of the patients reached iron >60 µg/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74–41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients.

Wilson A, Reyes E, Ofman J: Prevalence and outcomes of anemia in inflammatory bowel disease: a systematic review of the literature. Am J Med 2004;116(suppl 7A):44S–49S.
Gasche C, Lomer MC, Cavill I, Weiss G: Iron, anaemia, and inflammatory bowel diseases. Gut 2004;53:1190–1197.
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T: IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004;113:1271–1276.
Ganz T: Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783–788.
Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090–2093.
Fleming MD: The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Hematology Am Soc Hematol Educ Program 2008;151–158.
Schroder O, Mickisch O, Seidler U, de Weerth A, Dignass AU, Herfarth H, Reinshagen M, Schreiber S, Junge U, Schrott M, Stein J: Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease – a randomized, controlled, open-label, multicenter study. Am J Gastroenterol 2005;100:2503–2509.
Erichsen K, Ulvik RJ, Nysaeter G, Johansen J, Ostborg J, Berstad A, Berge RK, Hausken T: Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scand J Gastroenterol 2005;40:1058–1065.
Qunibi WY, Martinez C, Smith M, Benjamin J, Mangione A, Roger SD: A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients. Nephrol Dial Transplant 2011;26:1599–1607.
Srigiridhar K, Nair KM, Subramanian R, Singotamu L: Oral repletion of iron induces free radical mediated alterations in the gastrointestinal tract of rat. Mol Cell Biochem 2001;219:91–98.
Carrier J, Aghdassi E, Platt I, Cullen J, Allard JP: Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis. Aliment Pharmacol Ther 2001;15:1989–1999.
Erichsen K, Hausken T, Ulvik RJ, Svardal A, Berstad A, Berge RK: Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease. Scand J Gastroenterol 2003;38:543–548.
De Silva AD, Tsironi E, Feakins RM, Rampton DS: Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial. Aliment Pharmacol Ther 2005;22:1097–1105.
Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, Sambuelli AM, D’Haens G, Gasche C: A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (Ferinject®) randomized controlled trial. Am J Gastroenterol 2008;103:1182–1192.
Van Wyck DB, Martens MG, Seid MH, Baker JB, Mangione A: Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial. Obstet Gynecol 2007;110:267–278.
Breymann C, Gliga F, Bejenariu C, Strizhova N: Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia. Int J Gynaecol Obstet 2008;101:67–73.
Tagboto S, Cropper L, Turner J, Pugh-Clarke K: The efficacy of a single dose of intravenous ferric carboxymaltose (Ferinject®) on anaemia in a pre-dialysis population of chronic kidney disease patients. J Ren Care 2009;35:18–23.
Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Mori C, von Eisenhart Rothe B, Pocock S, Poole-Wilson PA, Ponikowski P: Rationale and design of Ferinject® assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail 2009;11:1084–1091.
Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P: Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436–2448.
Qunibi WY: The efficacy and safety of current intravenous iron preparations for the management of iron-deficiency anaemia: a review. Arzneimittelforschung 2010;60:399–412.
Evstatiev R, Marteau P, Iqbal T, Khalif IL, Stein J, Bokemeyer B, Chopey IV, Gutzwiller FS, Riopel L, Gasche C: FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology 2011;141:846–853.e1-2.
Wilson A, Yu HT, Goodnough LT, Nissenson AR: Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature. Am J Med 2004;116(suppl 7A):50S–57S.
Gasche C: Complications of inflammatory bowel disease. Hepatogastroenterology 2000; 47:49–56.
Pizzi LT, Weston CM, Goldfarb NI, Moretti D, Cobb N, Howell JB, Infantolino A, Dimarino AJ, Cohen S: Impact of chronic conditions on quality of life in patients with inflammatory bowel disease. Inflamm Bowel Dis 2006;12:47–52.
Wells CW, Lewis S, Barton JR, Corbett S: Effects of changes in hemoglobin level on quality of life and cognitive function in inflammatory bowel disease patients. Inflamm Bowel Dis 2006;12:123–130.
Stein J, Hartmann F, Dignass AU: Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol 2010;7:599–610.
Werner T, Wagner SJ, Martinez I, Walter J, Chang JS, Clavel T, Kisling S, Schuemann K, Haller D: Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Gut 2011;60:325–333.
Lomer MC, Kodjabashia K, Hutchinson C, Greenfield SM, Thompson RP, Powell JJ: Intake of dietary iron is low in patients with Crohn’s disease: a case-control study. Br J Nutr 2004;91:141–148.
Semrin G, Fishman DS, Bousvaros A, Zholudev A, Saunders AC, Correia CE, Nemeth E, Grand RJ, Weinstein DA: Impaired intestinal iron absorption in Crohn’s disease correlates with disease activity and markers of inflammation. Inflamm Bowel Dis 2006;12:1101–1106.
Kociol RD, Newby LK: Ferric carboxymaltose improved symptoms and quality of life in patients with chronic heart failure and iron deficiency. Ann Intern Med 2010;152:JC4–JC5.
Szczech LA, Bregman DB, Harrington RA, Morris D, Butcher A, Koch TA, Goodnough LT, Wolf M, Onken JE: Randomized evaluation of efficacy and safety of ferric carboxymaltose in patients with iron deficiency anaemia and impaired renal function (REPAIR-IDA): rationale and study design. Nephrol Dial Transplant 2010;25:2368–2375.
Schaefer RM, Khasabov NN, Todorov NG, et al: The efficacy and safety of intravenous ferric carboxymaltose compared to iron sucrose in haemodialysis patients with iron deficiency anaemia. 45th Congress of the European Renal Association and the European Dialysis and Transplant Association, Stockholm, May 10–13, 2008, abstract Mp375.
Qunibi M: Safety and tolerability profile of ferric carboxymaltose (FCM), a new high dose intravenous iron, across ten multi-center clinical trials. 40th Annual Meeting of the American Society of Nephrology, San Francisco, November 2–5, 2007, poster abstract.
Chandler G, Harchowal J, Macdougall IC: Intravenous iron sucrose: establishing a safe dose. Am J Kidney Dis 2001;38:988–991.
Fleming RE, Sly WS: Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad Sci USA 2001;98:8160–8162.
Katsanos K, Cavalier E, Ferrante M, Van Hauwaert V, Henckaerts L, Schnitzler F, Katsaraki A, Noman M, Vermeire S, Tsianos EV, Rutgeerts P, Chapelle JP, Van Assche G: Intravenous iron therapy restores functional iron deficiency induced by infliximab. J Crohns Colitis 2007;1:97–105.
Domenech E, Manosa M, Masnou H, Navarro M, Garcia-Planella E, Bernal I, Gassull MA: Infliximab for the treatment of chronic anemia in Crohn’s disease. Am J Gastroenterol 2005;100:496.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.